Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.27.1 (RNase)
16,360 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has long been known that lesions of the hypothalamus lead to female sexual precocity. While an increased production of luteinizing hormone-releasing hormone (LHRH), the neurohormone that controls sexual development, appears to mediate the advancement of puberty induced by these lesions, little is known about the mechanism(s) by which hypothalamic injury activates LHRH secretion. Since brain lesions result in accumulation of neurotrophic/mitogenic activities in the injured area, we tested the hypothesis that transforming growth factor alpha (TGF-alpha), a mitogenic polypeptide recently shown to stimulate LHRH release, is produced in response to hypothalamic injury and mediates the effect of the lesion on puberty. Radiofrequency lesions of the preoptic area-anterior hypothalamic area (POA-AHA) of 22-day-old female rats resulted in precocious puberty within 7 days after the operation. RNA blot hybridization revealed that lesion-induced puberty was preceded by an increase in TGF-alpha mRNA levels in the POA-AHA. Epidermal growth factor (EGF) mRNA was undetectable in both intact and lesioned hypothalami. TGF-alpha mRNA levels, quantitated by RNase protection assays, were 3.5-fold greater in lesioned animals approaching puberty than in age-matched controls. Immunohistochemical studies, utilizing single- and double-staining procedures, demonstrated the presence of TGF-alpha precursor-like immunoreactivity in reactive astrocytes surrounding the lesion site. Hybridization histochemistry showed increased TGF-alpha mRNA expression in cells of the same area, further implicating reactive astrocytes as a site of TGF-alpha synthesis. The actions of TGF-alpha are mediated by its interaction with EGF receptors. Continuous infusion of RG-50864, an inhibitor of EGF receptor kinase activity, at the site of injury prevented the advancement of puberty induced by the lesion. These results suggest that TGF-alpha acting via EGF-like receptors contributes to the acceleration of puberty induced by anterior hypothalamic lesions. They also indicate that activation of TGF-alpha gene expression in glial cells is a component of the hypothalamic response to injury.
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PMID:Transforming growth factor alpha contributes to the mechanism by which hypothalamic injury induces precocious puberty. 194 96

It has recently been shown that GH increases the number of available hepatic receptors for epidermal growth factor (EGF). In the present study the effects of the sexually dimorphic plasma GH pattern (higher pulsatility in male rats) on hepatic EGF binding and EGF receptor mRNA concentration were investigated. The specific binding of [125I]EGF to purified liver membranes was about 2-fold higher in male rats than in females on days 35, 50, and 80 of life. EGF receptor mRNA levels, as determined by an RNase protection solution hybridization assay, were higher in males only on days 47-50. Hypophysectomy on day 50 reduced the EGF receptor mRNA concentration to a level that did not differ between male and female rats. In hypophysectomized rats of both sexes, intermittent GH treatment (sc injections every 12 h for 7 days) enhanced hepatic EGF receptor mRNA concentrations to normal male levels, while continuous GH administration was less effective. Northern blot analysis indicated that transcripts with apparent sizes of 9.5 and 6.6 kilobases were dependent on the plasma GH pattern. Intermittent iv GH replacement therapy for 5 days given at 3-h intervals by an automatic iv infusion system increased the hepatic EGF receptor mRNA concentration as well as specific EGF binding, whereas continuous iv GH infusion was ineffective. These results show that a pulsatile plasma GH pattern, similar to that of male rodents, is markedly more effective in enhancing hepatic EGF receptor mRNA levels and EGF binding than a continuous feminine GH pattern. These results are consistent with a pretranslatory stimulation of EGF receptor synthesis by pulsatile GH.
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PMID:Plasma growth hormone pattern regulates epidermal growth factor (EGF) receptor messenger ribonucleic acid levels and EGF binding in the rat liver. 279 83

Human epidermal growth factor (EGF) receptor mRNA was detected in cryopreserved tissue sections adherent to whole glass slides using in situ reverse transcriptase polymerase chain reaction. EGF receptor cDNA was synthesized in situ by reverse transcription using an EGF receptor-specific oligonucleotide primer. In situ polymerase chain reaction amplification in the presence of digoxigenin-11-dUTP and subsequent binding with an antidigoxigenin antibody conjugated to alkaline phosphatase allowed direct visualization. Because DNase, RNase, or proteinase K are not required, tissue integrity is maintained. EGF receptor mRNA is expressed in the basal layer of normal human skin epithelium and is significantly overexpressed in squamous cell tumor specimens, which is consistent with conventional analysis of EGF receptor expression. The assay is semiquantitative, quicker, more sensitive, and void of the nonspecific binding associated with in situ hybridization. In situ reverse transcriptase polymerase chain reaction using whole glass slides is ideally suited for detecting moderate to infrequently expressed transcripts in biopsy specimens.
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PMID:Detection of epidermal growth factor receptor mRNA in tissue sections from biopsy specimens using in situ polymerase chain reaction. 808 54

Diversity of cell lineages within glandular organs is generated postnatally by differentiation of committed progenitor cells. Fundamental regulatory aspects of this process are not understood. The mouse submandibular salivary gland (SSG) served as model to assess the role of epidermal growth factor (EGF) receptor signaling during emergence of cell lineage diversity. Temporal fluctuations in EGF receptor mRNA levels coincident with crucial differentiative cell lineage transitions were revealed by RNase protection analyses. Between days 2 and 5, when proacinar cells are maturing and striated duct cells emerge, EGF receptor mRNA levels were highest and all differentiating cells exhibited EGF receptor immunoreactivity. EGF receptor mRNA levels then declined sharply and immunoreactivity became confined to ductal cells. At day 11 in male mice, and days 11 and 16 in females, a second increase in EGF receptor mRNA was detected coincident with emergence of granular convoluted tubule (GCT) cells. With completion of androgen-dependent GCT cell differentiation at the onset of puberty, EGF receptor mRNA levels and intensity of immunoreactivity decreased. Androgen effects on EGF receptor mRNA or immunoreactivity could not be detected. These temporally distinct patterns of EGF receptor expression suggest that this signaling pathway is a mechanism of potential importance in emergence of cell lineage diversity in a glandular organ.
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PMID:Emergence of salivary gland cell lineage diversity suggests a role for androgen-independent epidermal growth factor receptor signaling. 767 40

Evidence has shown that epidermal growth factor (EGF), transforming growth factor-alpha (TGF alpha) and their receptors (EGF receptors) are present in the anterior pituitary, indicating that the growth factors are synthesized in situ and act locally. Studies have demonstrated that EGF could stimulate the hypothalamus-pituitary-adrenal (HPA) cortex axis, particularly at the pituitary level in vivo and in vitro, and also stimulate TGF alpha messenger RNA (mRNA) expression in cultured bovine pituitary cells. Recently, our studies have demonstrated that some stresses up-regulated EGF mRNA expression in the anterior pituitary, as detected by ribonuclease protection assay, further indicating the possible roles of EGF in the stress response. However, little is yet known about the sources and targets (sites of EGF receptors) of the growth factors in the pituitary. Therefore, this study was designed to localize EGF and TGF alpha mRNA and their receptors as well as to assess the effects of cold stress (CS) on their expression in the subsets of pituitary cells. In situ hybridization immunocytochemistry coupled with immunocytochemistry and dual immunocytochemistry studies revealed the presence of 1) EGF mRNA in somatotropes and gonadotropes; 2) TGF alpha mRNA in somatotropes, gonadotropes, and lactotropes; and 3) EGF receptors in all subsets of pituitary cells. CS (30 min) induced the expression of EGF mRNA in corticotropes and thyrotropes. EGF expression was not altered in somatotropes and gonadotropes. No significant changes were detected in TGF alpha mRNA expression in the pituitary cells after 30 min of CS. Expression of EGF receptors was also increased after 30 min of CS. This resulted from increases in EGF receptor-labeled cells among thyrotropes and gonadotropes. The cold stress-induced expression of EGF mRNA in corticotropes and thyrotropes fits with their overall activation after this type of stress. The increase in EGF receptor-labeled cells among thyrotropes may point to an important autocrine role for EGF in maintaining TSH responses to cold. On the other hand, the significance of EGF receptor up-regulation in gonadotropes (FSH-containing cells) caused by CS remains unknown.
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PMID:Epidermal growth factor and transforming growth factor-alpha messenger ribonucleic acids and their receptors in the rat anterior pituitary: localization and regulation. 772 Jun 77

The isolation of a cDNA corresponding to a portion (amino acid 943 to 1073) of the cytoplasmic domain of the mouse EGF receptor surrounding the auto phosphorylation sites was obtained by using the reverse transcriptase polymerase chain reaction (RT-PCR) approach. Deduced amino acid sequence of mouse EGF receptor (EGFr) shows a 92% and 76% homology to corresponding regions in the human and the chicken EGFr, respectively. This cDNA was used to develop a sensitive RNase protection assay to investigate EGF receptor mRNA expression in mouse C3H teratoma derived cell lines with increased tumorigenic properties which display a progressive decrease of EGF binding and response. The results show that increased tumorigenicity was not accompanied by a change in EGF receptor mRNA expression. Moreover, they indicate that the RNase protection assay developed using the probe described here is a sensitive approach to investigate EGF receptor expression in murine cells.
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PMID:Nucleotide sequence of the C-terminal region of the mouse epidermal growth factor receptor and expression in teratoma-derived cell lines with increased tumorigenic properties. 776 4

Epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) are mitogenic to the intestinal epithelium. To further clarify their role in the developing human fetal gut, their expression was studied in fetuses at 15 to 20 wk of gestation. TGF-alpha mRNA was present throughout the gastrointestinal tract, most abundantly in the duodenum. EGF mRNA could be detected only with ribonuclease protection assay and reverse transcription-polymerase chain reaction analysis. The effect of EGF and TGF-alpha on TGF-alpha mRNA expression was studied by culturing explants of fetal jejunum, ileum, and colon for 7 d in Leibowitz L-15 medium supplemented with 100 micrograms/L of either EGF or TGF-alpha. EGF receptor-like immunoreactivity was detected in both the villi and the crypts. In the jejunum, exogenous EGF up-regulated TGF-alpha mRNA 3-fold. However, exogenous TGF-alpha reduced its own mRNA by 40%. No mature 6-kD TGF-alpha was detected in the culture medium by Western blotting, but precursor forms of approximately 30 and 68 kD were present. The ileum and colon did not respond to either growth factor. Besides the gut, TGF-alpha was expressed in the gallbladder, salivary gland, adrenals, brain, kidney, liver, and placenta. The data imply an important role for TGF-alpha and EGF in the developing intestine.
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PMID:Transforming growth factor-alpha and epidermal growth factor expression in human fetal gastrointestinal tract. 851 Oct 20

There is increasing evidence that activation of the insulin-like growth factor I (IGF-I) receptor plays a major role in the control of cellular proliferation of many cell types. We studied the mitogenic effects of IGF-I, IGF-II, and epidermal growth factor (EGF) on growth-arrested HT-3 cells, a human cervical cancer cell line. All three growth factors promoted dose-dependent increases in cell proliferation. In untransformed cells, EGF usually requires stimulation by a "progression" factor such as IGF-I, IGF-II, or insulin (in supraphysiologic concentrations) in order to exert a mitogenic effect. Accordingly, we investigated whether an autocrine pathway involving IGF-I or IGF-II participated in the EGF-induced mitogenesis of HT-3 cells. With the RNase protection assay, IGF-I mRNA was not detected. However, IGF-II mRNA increased in a time-dependent manner following EGF stimulation. The EGF-induced mitogenesis was abrogated in a dose-dependent manner by IGF-binding protein 5 (IGFBP-5), which binds to IGF-II and neutralizes it. An antisense oligonucleotide to IGF-II also inhibited the proliferative response to EGF. In addition, prolonged, but not short-term, stimulation with EGF resulted in autophosphorylation of the IGF-I receptor, and coincubations with both EGF and IGFBP-5 attenuated this effect. These data demonstrate that autocrine secretion of IGF-II in HT-3 cervical cancer cells can participate in EGF-induced mitogenesis and suggest that autocrine signals involving the IGF-I receptor occur "downstream" of competence growth factor receptors such as the EGF receptor.
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PMID:Insulin-like growth factor II mediates epidermal growth factor-induced mitogenesis in cervical cancer cells. 861 25

Recombinant human ribonuclease 1 (RNase 1) was chemically linked to recombinant human epidermal growth factor (EGF). The EGF-RNase conjugate showed dose-dependent cytotoxicity for EGF receptor-overexpressing A431 and TE-8 human squamous carcinoma cells with an IC50 of 2 x 10(-7)M and 10(-6)M, respectively, whereas the IC50 of RNase alone was almost 10(-4)M. An unconjugated mixture of EGF and RNase had no greater effect than RNase alone. The conjugate showed no detectable cytotoxicity against EGF receptor-deficient small cell lung cancer cells (H69). Addition of excess EGF in the medium protected A431 cells from the EGF-RNase conjugate cytotoxicity. The cytotoxicity of the EGF-RNase conjugate was positively correlated with the EGF receptor numbers of each cell line. The chimeric toxin composed of only human proteins might be a more useful anti-cancer agent with less immunogenicity than the conventional chimeric toxins.
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PMID:Epidermal growth factor receptor-dependent cytotoxicity for human squamous carcinoma cell lines of a conjugate composed of human EGF and RNase 1. 863 16

Peptide growth factors likely play an important role in cardiac development, but growth factors which inhibit or prevent differentiation in cardiac myocytes are largely unknown. Using immunocytochemistry, Western and Northern blotting, and RNase protection assays, we demonstrate that epidermal growth factor (EGF) significantly inhibits differentiation and promotes proliferation in cultured human fetal ventricular cardiac myocyte cell lines. In enriched cell lines and in a pure myocyte cell strain, EGF inhibited increases in immunoreactive sarcomeric actin and sarcomeric myosin heavy chain (SMHC) normally seen after serum withdrawal. In the pure myocyte strain, EGF induced a cardiomyoblastic phenotype; i.e., it caused a complete loss of detectable sarcomeric proteins in the majority of cells; it was also mitogenic. EGF inhibited expression of cardiac alpha-actin and SMHC mRNAs, but inhibition of SMHC expression was predominantly of the beta-MHC isoform. Removal of EGF was followed by reexpression of sarcomeric proteins. Blocking the EGF receptor (EGFR) with monoclonal anti-receptor antibody completely abolished the dedifferentiating effects of EGF and also significantly reduced the mitogenic effect of the peptide. The results indicate that activation of the EGFR both inhibits differentiation and promotes proliferation of human fetal ventricular myocytes in vitro. These findings suggest an important role for EGF in human cardiac differentiation and development.
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PMID:Epidermal growth factor promotes a cardiomyoblastic phenotype in human fetal cardiac myocytes. 891 16


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